The term "autoimmune disease" as used herein includes all of the diseases caused by an immune response such as an autoantibody or cell-mediated immunity to an autoantigen and the like. Examples of the diseases as described above include, for example, chronic rheumatoid arthritis, systemic lupus erythematosus, scleroderma, mixed connective tissue disease, polyarteritis nodosa, polymyositis/dermatomyositis, Sjogren's syndrome, Bechet's disease, multiple sclerosis, autoimmune diabetes, Hashimoto's disease, psoriasis, primary myxedema, pernicious anemia, myasthenia gravis, ulcerative colitis, chronic active hepatitis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura and the like.
In general for autoimmune diseases, it has been considered that the expression of mechanism symptoms is based on hereditary factors or environmental factors. That is to say, the initiation of the autoimmune disease is, for example,a virus infection and then an immunity disorder leads to autoimmune diseases. Up to now, symptomatic treatment using non-steroidal anti-inflammatory drugs has been mainly employed in order to control the inflammatory symptoms as a method of medical treatment for the diseases noted above. However, it is presently impossible to intrinsically cure, from the standpoint of side-effects, the disease by symptomatic treatment using non-steroidal anti-inflammatory drugs even if the effect of the drug has been favorably evaluated. Under such circumstances, a treatment method to intrinsically improve an aberrant immune system and immune enhancement based on an immunomodulating action and/or a cell adhesion inhibiting action is desireable.
As a medicament having an immunomodulating action, for example, D-penicillamine and Sulfasalazine have been described in Annual reports in medicinal chemistry (Annu. Rep. Med. Chem), Vol.21, pp.201-210(1986). It is also expected that a medicament which inhibits the appearance of cell adhesion molecules on the cell surface is useful as an agent for the treatment of autoimmune diseases. See example, Arthritis and Rheumatism, Vol 36, No.2, pp.147-157(1993); and Clinical Immunology, Vol.26, No.2, pp.190-197(1994).
A derivative of 4H-1-benzopyran-4-one or a salt thereof, which is represented by the general formula [1] is known and has anti-inflammatory analgesic, antipyretic, antiarthristic and antiallergic actions, [Japanese Patent Application Kokai No.2 (1990)-49778], and has a supressive effect on the production of interleukins 1 and 6, which is useful for prevention and treatment of diseases caused by abnormal production of interleukins 1 and 6, Journal of Pharamacobio Dynamics (J. Pharmacobio-Dyn. ), Vol. 15, pp. 649-655 (1992). However, it is not known that a derivative of 4H-1-benzopyran-4-one or a salt thereof is capable of improving abnormal immunity or aberrant enhancement of cell adhesion based on an immunomodulating and/or cell adhesion inhibiting action.
So far, D-penicillamine, lobenzarit and the like have been used as immunomodulating agents or agents for autoimmune diseases. But there are few of these agents, and the effects against immunodeficiency are not sufficient. W hen these drugs have been used for long-term treatment, the effect of these drugs may be diminished. These drugs are never satisfactory as immunomodulating agents or agents for autoimmune diseases. Cell adhesion inhibitors have been researched for use as clinical drugs [Drug News & Perspectives, Vol.5, No.6, pp.331-337(1992)]. Hence, the development of an agent which has a superior effect against immunodeficiency and a suppressive effect against aberrant enhancement of cell adhesion molecules, is expected to function a drug for treating and preventing autoimmune diseases.
It is an object of the present invention to provide an immunomodulating agent, a cell adhesion inhibiting agent and an agent for treating and preventing autoimmune diseases.